1. Field of the Invention
The present invention concerns a method to inactivate viruses in cell-containing compositions, for example, in whole blood or red blood cell concentrates, without incurring substantial disruption or inactivation of cells, for example, without adversely affecting red blood cell structure or function, by using a photoactive compound, for example, a phthalocyanine, together with light exposure.
2. Description of Related Art
Nature of the Concept
Substantial progress has been made in reducing the viral infectivity of whole blood and its components through improved donor selection and donor blood screening procedures. Despite this progress, there is a continued risk of transmission of viruses including hepatitis viruses and human immunodeficiency viruses (HIV) by whole blood and blood products.
Viral risk has been considerably reduced and possibly eliminated in coagulation factor concentrates through the application of virucidal procedures during the course of manufacture (Prince, A. M., Horowitz, B., Horowitz, M. S., Zang, E., "The Development of Virus-Free Labile Blood Derivatives-A Review", Eur. J. Eoidemiol., 1987;3:103-118 and Mannucci, P. M., Colombo, M., "Virucidal Treatment of Clotting Factor Concentrates", The Lancet, 1988;782-785). By contrast, the development of virucidal processes applicable to cell components, i.e., blood cell fractions such as red blood cells or platelets, has been slow, both because cells are more fragile than proteins, and cells serve to harbor and protect virus against inactivation. Nonetheless, if virus transmission by whole blood or blood components is to be eliminated, effective virus removal or potent virucidal methods applicable to blood cells will be required. Since both red blood cells or platelets are non-replicating, approaches directed toward nucleic acid modification might offer the required specificity.
It is important to recognize in assessing virucidal procedures that virus will be present in cell-containing solutions in multiple forms: virus free of the cell; formed virus associated with the cell; functional, but unpackaged viral nucleic acid within the cell; and viral nucleic acid integrated into the cell genome. Each form should be considered infectious and capable of causing viral disease in vivo. Virucidal methods which inactivate virus in one form, e.g., cell-free virus, may not inactivate virus in other forms, e.g., cell-associated forms. Additionally, the presence of cells is known to inhibit the action of both physical and chemical approaches to virus inactivation. Cells compete for added virucidal reagents and absorb radiation which otherwise would be virucidal. Thus, for example, while ultraviolet irradiation is highly virucidal in salt solutions or in dilute protein solution, the degree of virucidal activity is incomplete when treating cell-containing solutions. Furthermore, in this context, it is not sufficient to inactivate virus alone; rather, it is necessary to do so with sufficient vigor that viral infectivity is eliminated without deleterious effects to the valuable cell components, e.g., red blood cells.
Most virucidal procedures which have been developed, e.g., pasteurization or solvent/detergent treatment, cannot be applied to blood cell preparations without damaging the cells and rendering them unfit for transfusion.
Heretofore, it has not been possible to prepare virus sterilized forms of whole blood or red cell concentrates or platelet concentrates where at least 10.sup.4 infectious units (ID.sub.50) and preferably .gtoreq.10.sup.6 ID.sub.50 of both intracellular and extracellular virus were inactivated without adversely affecting the cells and/or without using highly toxic agents.